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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2016

Open Access 01-12-2016 | Research

Increased tauopathy drives microglia-mediated clearance of beta-amyloid

Authors: Wesley Chen, Edsel A. Abud, Stephen T. Yeung, Anita Lakatos, Trevor Nassi, Jane Wang, David Blum, Luc Buée, Wayne W. Poon, Mathew Blurton-Jones

Published in: Acta Neuropathologica Communications | Issue 1/2016

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Abstract

Alzheimer disease is characterized by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Emerging studies suggest that in neurodegenerative diseases, aggregation of one protein species can promote other proteinopathies and that inflammation plays an important role in this process. To study the interplay between Aβ deposition, tau pathology, and microgliosis, we established a new AD transgenic mouse model by crossing 5xfAD mice with Thy-Tau22 transgenic mice. The resulting ‘T5x’ mice exhibit a greater than three-fold increase in misfolded and hyperphosphorylated tau and further substantiates the hypothesis that Aβ accelerates tau pathology. Surprisingly, T5x mice exhibit a 40-50 % reduction in Aβ plaque load and insoluble Aβ species when compared with aged-matched 5xfAD littermates. T5x mice exhibit significant changes in cytokine production, an almost doubling of microglial number, and a dramatic shift in microglia activation state. Furthermore, T5x microglia exhibit increased phagocytic capacity that enhances the clearance of insoluble Aβ and decreasing plaque load. Therefore, our results suggest that strategies to increase the phagocytic ability of microglia can be employed to reduce Aβ and that tau-induced changes in microglial activation state can promote the clearance of Aβ.
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Metadata
Title
Increased tauopathy drives microglia-mediated clearance of beta-amyloid
Authors
Wesley Chen
Edsel A. Abud
Stephen T. Yeung
Anita Lakatos
Trevor Nassi
Jane Wang
David Blum
Luc Buée
Wayne W. Poon
Mathew Blurton-Jones
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2016
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-016-0336-1

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